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Anti-HIV Drugs for Treating Infants Who Acquired HIV Infection at Birth

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ClinicalTrials.gov Identifier: NCT00102960
Recruitment Status : Completed
First Posted : February 7, 2005
Results First Posted : November 30, 2018
Last Update Posted : November 30, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: Abacavir sulfate
Drug: Didanosine
Drug: Efavirenz
Drug: Lamivudine
Drug: Lopinavir/Ritonavir
Drug: Nevirapine
Drug: Zidovudine
Enrollment 377
Recruitment Details  
Pre-assignment Details The results are presented for only 377 participants that were enrolled into the three arms (ART-Def 125, ART-40W 126 and ART-96W 126).
Arm/Group Title ART-Deferred Early ART up to 40 Weeks Early ART up to 96 Weeks
Hide Arm/Group Description

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Period Title: Overall Study
Started 125 126 126
Completed 95 103 98
Not Completed 30 23 28
Reason Not Completed
Death             23             11             11
Lost to Follow-up             6             12             16
Withdrawal by Subject             1             0             1
Arm/Group Title Deferred Therapy Early Therapy up to 40 Weeks Early Therapy up to 96 Weeks Total
Hide Arm/Group Description

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Total of all reporting groups
Overall Number of Baseline Participants 125 126 126 377
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Weeks
Number Analyzed 125 participants 126 participants 126 participants 377 participants
7.1
(6.4 to 8.9)
7.4
(6.6 to 8.7)
7.5
(6.6 to 9.0)
7.3
(6.5 to 8.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 125 participants 126 participants 126 participants 377 participants
Female
70
  56.0%
76
  60.3%
74
  58.7%
220
  58.4%
Male
55
  44.0%
50
  39.7%
52
  41.3%
157
  41.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
South Africa Number Analyzed 125 participants 126 participants 126 participants 377 participants
125 126 126 377
1.Primary Outcome
Title Time to Failure of First Line Therapy or Death
Hide Description To compare time to failure of first line ART (due to clinical, virological or immunological disease progression, or regimen-limiting ART toxicities) or death among three randomized arms (infants who receive early ART in Arms 2 and 3 and infants in whom ART is deferred until clinical or immunological disease progression in Arm 1) during the study (up to 4.8 years). The number of participants experiencing the events did not reach the 50% survival and thus median time-to-event is not be presented. Therefore we report the number of participants experiencing the events per Arm.
Time Frame From date of randomization up to failure of first-line therapy or death from any cause, whichever came first, assessed up to 4.8 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
In the analysis of failure of first-line therapy, children enrolled in the ART-Deferred group were used as the reference category in the hazard ratio analysis.
Arm/Group Title Deferred Therapy Early Therapy up to 40 Weeks Early Therapy up to 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 125 126 126
Measure Type: Count of Participants
Unit of Measure: Participants
48
  38.4%
32
  25.4%
26
  20.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Deferred Therapy, Early Therapy up to 40 Weeks
Comments Statistical analysis compares early therapy 40 weeks (ART-40W) relative to deferred therapy (ART-Def)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.38 to 0.93
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Deferred Therapy, Early Therapy up to 96 Weeks
Comments Statistical analysis compares early therapy 96 weeks (ART-96W) relative to deferred therapy (ART-Def)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.27 to 0.76
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Participants Who Experienced Immunological Failure Defined as Failure of CD4% to Reach 20% or CD4% Falls Below 20% on Two Occasions, Within 4 Weeks, at Any Time After the First 24 Weeks of Therapy (Initial Therapy or Restart)
Hide Description This was part of the primary outcome measure above. The primary outcome was a composite endpoint. The primary outcome analysis only considered the initially enrolled children that were 377 in total (ART-Deferred n=125, Early therapy 40 weeks n=126 and Early therapy 96 weeks n=126). This was part of the primary outcome measure that was a composite endpoint.
Time Frame This outcome was assessed from the date of randomization to immunological failure. Immunological failure was assessed in the entire study duration of 4.8 years.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Deferred Therapy Early ART for 40 Weeks Early Therapy for 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily

Overall Number of Participants Analyzed 125 126 126
Measure Type: Count of Participants
Unit of Measure: Participants
9
   7.2%
14
  11.1%
11
   8.7%
3.Primary Outcome
Title Number of Participants Who Experienced Regimen-limiting ART Drug Toxicity
Hide Description Development of toxicity requiring more than one drug substitution within the same class or a switch to a new class of drugs (regimen-limiting toxicity failure) or requiring a permanent treatment discontinuation. This was part of the primary outcome measure that was a composite endpoint.
Time Frame Regimen limiting drug toxicity was monitored from randomization up to the entire study duration of 4.8 years.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Deferred Therapy Early Therapy 40 Weeks Early Therapy 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 125 126 126
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
4.Primary Outcome
Title Number of Participants Who Experienced Clinical Failure (Defined as Development of Severe CDC Stage B or Stage C Disease.) on Therapy.
Hide Description This included development of severe CDC Stage B or Stage C disease.This was part of the primary outcome measure that was a composite endpoint
Time Frame Clinical failure on therapy was assessed at each visit for the entire study duration of 4.8 years.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Deferred Therapy Early Therapy 40 Weeks Early Therapy 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 125 126 126
Measure Type: Count of Participants
Unit of Measure: Participants
8
   6.4%
6
   4.8%
5
   4.0%
5.Primary Outcome
Title Number of Participants Who Experienced Virological Failure Defined as Confirmed HIV-1 RNA Value of at Least 10,000 Copies Per/ml Recorded on Two Consecutive Separate Occasions After 24 Weeks of Treatment (Initial Therapy or Restart)
Hide Description This was part of the primary outcome measure that was a composite endpoint that included confirmed HIV-1 RNA value of at least 10,000 copies per/ml recorded on two consecutive separate occasions after 24 weeks of treatment (initial therapy or restart).
Time Frame Virological failure was assessed from randomization through the entire study duration of 4.8 years.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Deferred Therapy Early Therapy 40 Weeks Early Therapy 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 125 126 126
Measure Type: Count of Participants
Unit of Measure: Participants
10
   8.0%
1
   0.8%
1
   0.8%
6.Secondary Outcome
Title Number of Children Experiencing Severe CDC Stage B or Stage C Disease or Death (Cumulative After 3.5 Years)
Hide Description The outcome measure is defined as a number because it represents the number of children that experienced severe CDC Stage B or Stage C disease or death as defined in the outcome measure title above
Time Frame Occurrence of severe CDC Stage B or Stage C disease or death (cumulative after 3.5 years), whichever came first, was assessed from randomization up to at least 3.5 years.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Deferred Therapy Early Therapy 40 Weeks Early Therapy 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 125 126 126
Measure Type: Count of Participants
Unit of Measure: Participants
41
  32.8%
28
  22.2%
21
  16.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Deferred Therapy, Early Therapy 40 Weeks
Comments Relative to ART-Def, ART-40W had a 13% difference in the cumulative probability of clinical disease progression or death at 3·5 years
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Proportion test
Comments [Not Specified]
Method of Estimation Estimation Parameter Kaplan-Meier Cummulative Probability
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
0.01 to 0.25
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Deferred Therapy, Early Therapy 96 Weeks
Comments Relative to ART-Def, ART-96W had a 13% difference in the cumulative probability of clinical disease progression or death at 3·5 years
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Proportion test
Comments [Not Specified]
Method of Estimation Estimation Parameter Kaplan-Meier Cummulative Probability
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
0.09 to 0.31
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Total Occurrence of Grade 3 or 4 Clinical Events
Hide Description This was a secondary outcome measure that assessed the total count of Grade 3 or 4 (clinical or laboratory) adverse events.
Time Frame 4.8 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis was only performed on the primary groups including a total of 377 participants
Arm/Group Title Deferred Therapy Early Therapy 40 Weeks Early Therapy 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 125 126 126
Measure Type: Number
Unit of Measure: Count of events
170 118 88
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Deferred Therapy, Early Therapy 40 Weeks, Early Therapy 96 Weeks
Comments The CHER study compared Grade 3 or 4 clinical event rates per 100 person-years between the three arms using Poisson regression modeling over the study duration of 4.8 years.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments This p-value compares event rates per 100 person-years across the three arms
Method Poisson Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate per 100 person years
Estimated Value 0
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Total Occurrence of Grade 3 or 4 Laboratory Events
Hide Description [Not Specified]
Time Frame From randomization up to 4.8 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Deferred Therapy Early Therapy 40 Weeks Early Therapy 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 125 126 126
Measure Type: Number
Unit of Measure: Count of events
35 44 33
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Deferred Therapy, Early Therapy 40 Weeks, Early Therapy 96 Weeks
Comments The event rates per 100 person years were compared across the three arms
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46
Comments [Not Specified]
Method Poisson regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate per 100 person years
Estimated Value 0
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time From Randomization to Starting or Needing to Start Continuous Therapy
Hide Description Time from randomization to starting (deferred therapy Arm) or needing to start continuous therapy (early therapy 40 or 96 weeks)
Time Frame 4.8 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Deferred Therapy Early Therapy 40 Weeks Early Therapy 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 125 126 126
Median (Full Range)
Unit of Measure: Weeks
20
(16 to 25)
33
(26 to 45)
70
(35 to 109)
10.Secondary Outcome
Title Number of Participants With Indicated Viral Resistance Mutations at the Time of Failure of First Line Therapy
Hide Description Resistance testing was performed on samples with a VL≥1000 c/ml together with the matched baseline sample, if available. Reverse transcriptase (NRTI and NNRTI) and protease (PI) inhibitor mutations were analysed using a validated in-house population-based sequencing assay and the IAS 2011 mutation list.
Time Frame 4.8 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Mutations presented descriptively were 1) Protease inhibitor mutations and 2) Met184Val mutations were reported. Only 32 participants with viral load above 1,000 copies/ml at their last visit while on treatment were analysed.
Arm/Group Title Deferred Therapy Early Therapy 40 Weeks Early Therapy 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 5 14 13
Measure Type: Count of Participants
Unit of Measure: Participants
PI mutations
1
  20.0%
1
   7.1%
0
   0.0%
Met184Val mutations
1
  20.0%
5
  35.7%
1
   7.7%
No mutations
3
  60.0%
8
  57.1%
12
  92.3%
11.Secondary Outcome
Title Time to Death Alone or Death Plus Life Threatening Stage C Events or HIV Events Associated With Permanent End-organ Damage.
Hide Description This was a composite endpoint in which the number of children experiencing the events is reported. The number of participants experiencing the events did not reach the 50% survival and thus median time-to-event is not be presented. Therefore, we report the number of participants experiencing the events per Arm.
Time Frame 4.8 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Deferred Therapy Early Therapy 40 Weeks Early Therapy 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 125 126 126
Measure Type: Count of Participants
Unit of Measure: Participants
34
  27.2%
18
  14.3%
13
  10.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Deferred Therapy, Early Therapy 40 Weeks
Comments The analysis compares ART-40W relative to the ART-Def arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
0.27 to 0.84
Estimation Comments Hazard rate reported above compares early therapy 40 weeks relative to the deferred therapy arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Deferred Therapy, Early Therapy 96 Weeks
Comments The analysis compares ART-96 Weeks relative to ART-Deferred
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.18 to 0.64
Estimation Comments The hazard ratio compares ART-96W relative to the ART-Def arm.
12.Secondary Outcome
Title Hospitalization Rates
Hide Description Hospitalisation rates in the three arms enrolled in the CHER study
Time Frame 4.8 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Deferred Therapy Early Therapy 40 Weeks Early Therapy 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 125 126 126
Measure Type: Number
Unit of Measure: Events per 100 person years
27.6 16.4 14.2
13.Secondary Outcome
Title Duration of Hospitalisation
Hide Description This is the total number of days spent in hospital by the participants and is reported per arm
Time Frame 4.8 years, the study duration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Deferred Therapy Early Therapy 40 Weeks Early Therapy 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 125 126 126
Measure Type: Number
Unit of Measure: Days
1018 533 414
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Deferred Therapy, Early Therapy 40 Weeks, Early Therapy 96 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments The p-value here compares the days spent in hospital across the three arms
Method Poisson regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Count of days
Estimated Value 0
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Time to First Hospitalization
Hide Description To compare time to first hospitalization in the three randomized arms (infants who received early ART in Arms 2 and 3 and those who received deferred ART in Arm 1). Not all participants were hospitalized and thus the upper limits could not be evaluated.
Time Frame From randomization up to 4.8 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Deferred Therapy Early Therapy 40 Weeks Early Therapy 96 Weeks
Hide Arm/Group Description:

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

Overall Number of Participants Analyzed 125 126 126
Median (Full Range)
Unit of Measure: Weeks
73.1 [1] 
(22.6 to NA)
NA [2] 
(184.4 to NA)
NA [2] 
(179.0 to NA)
[1]
Upper limit of median not estimable
[2]
The median is not estimable because the survival curve did not cross the 50% survival
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Deferred Therapy, Early Therapy 40 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.562
Confidence Interval (2-Sided) 95%
0.389 to 0.811
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Deferred Therapy, Early Therapy 96 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0038
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.583
Confidence Interval (2-Sided) 95%
0.405 to 0.840
Estimation Comments [Not Specified]
Time Frame 4.8 years, the study duration
Adverse Event Reporting Description Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
 
Arm/Group Title ART-Deferred Early ART up to 40 Weeks Early ART up to 96 Weeks
Hide Arm/Group Description

For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously.

Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday

Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily

Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2

Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight.

Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily.

All-Cause Mortality
ART-Deferred Early ART up to 40 Weeks Early ART up to 96 Weeks
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   23/125 (18.40%)      11/126 (8.73%)      11/126 (8.73%)    
Show Serious Adverse Events Hide Serious Adverse Events
ART-Deferred Early ART up to 40 Weeks Early ART up to 96 Weeks
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   79/125 (63.20%)      60/126 (47.62%)      53/126 (42.06%)    
Blood and lymphatic system disorders       
Anaemia  1  2/125 (1.60%)  2 2/126 (1.59%)  2 1/126 (0.79%)  1
Lymphadenitis  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Neutropenia  1  1/125 (0.80%)  1 2/126 (1.59%)  2 1/126 (0.79%)  1
Splenomegaly  1  0/125 (0.00%)  0 2/126 (1.59%)  2 0/126 (0.00%)  0
Thrombocytopenia  1  1/125 (0.80%)  1 1/126 (0.79%)  2 2/126 (1.59%)  2
Cardiac disorders       
Cardiac failure  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Myocarditis  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Congenital, familial and genetic disorders       
Cerebral palsy  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Ear and labyrinth disorders       
Hearing loss unilateral  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Gastrointestinal disorders       
Gastroenteritis  1  11/125 (8.80%)  12 5/126 (3.97%)  5 2/126 (1.59%)  4
Haematemesis  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Vomiting  1  2/125 (1.60%)  2 0/126 (0.00%)  0 1/126 (0.79%)  1
General disorders       
Accidental death  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Apparent death  1  2/125 (1.60%)  2 2/126 (1.59%)  2 0/126 (0.00%)  0
Death  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Fever  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Oedema  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Unknown cause of death  1  6/125 (4.80%)  6 2/126 (1.59%)  2 5/126 (3.97%)  5
Hepatobiliary disorders       
Hepatomegaly  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Liver failure  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Immune system disorders       
HIV wasting syndrome  1  1/125 (0.80%)  1 1/126 (0.79%)  1 0/126 (0.00%)  0
Infections and infestations       
Lymphadenopathy  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Abscess  1  1/125 (0.80%)  2 1/126 (0.79%)  1 1/126 (0.79%)  1
Bronchiolitis  1  5/125 (4.00%)  5 3/126 (2.38%)  3 3/126 (2.38%)  5
Bronchitis  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Bronchopneumonia  1  6/125 (4.80%)  8 4/126 (3.17%)  6 3/126 (2.38%)  3
Cellulitis  1  1/125 (0.80%)  1 2/126 (1.59%)  2 1/126 (0.79%)  1
Chickenpox  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Croup  1  1/125 (0.80%)  1 1/126 (0.79%)  2 1/126 (0.79%)  1
Cytomegalovirus encephalitis  1  1/125 (0.80%)  2 0/126 (0.00%)  0 0/126 (0.00%)  0
Cytomegalovirus hepatitis  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Dysentery  1  1/125 (0.80%)  1 1/126 (0.79%)  1 0/126 (0.00%)  0
Esophageal candidiasis  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Gastroenteritis  1  38/125 (30.40%)  53 22/126 (17.46%)  29 27/126 (21.43%)  31
Laryngotracheo bronchitis  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Lower respiratory tract infection  1  1/125 (0.80%)  2 0/126 (0.00%)  0 0/126 (0.00%)  0
Meningitis  1  6/125 (4.80%)  7 2/126 (1.59%)  2 2/126 (1.59%)  2
Miliary tuberculosis  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Oesophageal candidiasis  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Oral candidiasis  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Osteomyelitis chronic  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Otitis media  1  0/125 (0.00%)  0 1/126 (0.79%)  2 0/126 (0.00%)  0
Parotitis  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Pharyngitis  1  1/125 (0.80%)  1 1/126 (0.79%)  1 0/126 (0.00%)  0
Pharyngitis bacterial  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Pneumococcal pneumonia  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Pneumococcal Sepsis  1  1/125 (0.80%)  1 1/126 (0.79%)  1 0/126 (0.00%)  0
Pneumocystis carinii pneumonia  1  5/125 (4.00%)  6 1/126 (0.79%)  1 0/126 (0.00%)  0
Pneumonia  1  26/125 (20.80%)  34 18/126 (14.29%)  25 17/126 (13.49%)  20
Sepsis  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  2
Septicaemia  1  2/125 (1.60%)  2 0/126 (0.00%)  0 1/126 (0.79%)  1
Sinusitis  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
TB  1  4/125 (3.20%)  4 3/126 (2.38%)  3 1/126 (0.79%)  1
Tonsillitis  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Tuberculous bronchopneumonia  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Urinary tract infection  1  3/125 (2.40%)  3 4/126 (3.17%)  4 0/126 (0.00%)  0
Viral meningitis  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Injury, poisoning and procedural complications       
Burns  1  1/125 (0.80%)  1 2/126 (1.59%)  2 0/126 (0.00%)  0
Forearm fracture  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Fracture  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Fracture femur  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Poisoning  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Skull fracture  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Investigations       
AST increased  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Gamma GT increased  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Hyperkalaemia  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Lipase increased  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Transaminases increased  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Metabolism and nutrition disorders       
Decreased appetite  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Failure to thrive  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Hyperkalaemia  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Hypernatremia  1  0/125 (0.00%)  0 2/126 (1.59%)  3 3/126 (2.38%)  3
Hypokalaemia  1  1/125 (0.80%)  1 0/126 (0.00%)  0 1/126 (0.79%)  1
Kwashiorkor  1  1/125 (0.80%)  1 0/126 (0.00%)  0 1/126 (0.79%)  1
Lactic acidosis  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Obesity  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Nervous system disorders       
Encephalopathy  1  1/125 (0.80%)  1 1/126 (0.79%)  1 0/126 (0.00%)  0
Febrile seizure  1  1/125 (0.80%)  1 2/126 (1.59%)  2 0/126 (0.00%)  0
Focal seizures  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Generalised tonic-clonic seizure  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Pneumococcal meningitis  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Seizures  1  1/125 (0.80%)  1 1/126 (0.79%)  1 0/126 (0.00%)  0
Renal and urinary disorders       
Acute renal failure  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Reproductive system and breast disorders       
Rectovaginal fistula  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Aspiration  1  0/125 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0
Aspiration pneumonitis  1  0/125 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1
Pneumonia  1  2/125 (1.60%)  2 2/126 (1.59%)  2 0/126 (0.00%)  0
Pneumonitis  1  1/125 (0.80%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0
Skin and subcutaneous tissue disorders       
Dermatitis  1  0/125 (0.00%)  0 2/126 (1.59%)  2 0/126 (0.00%)  0
1
Term from vocabulary, MedDRA 10.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ART-Deferred Early ART up to 40 Weeks Early ART up to 96 Weeks
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   123/125 (98.40%)      122/126 (96.83%)      125/126 (99.21%)    
Blood and lymphatic system disorders       
Lymphadenopathy  1  38/125 (30.40%)  46 52/126 (41.27%)  64 39/126 (30.95%)  42
Neutropenia  1  5/125 (4.00%)  7 9/126 (7.14%)  10 14/126 (11.11%)  17
Splenomegaly  1  32/125 (25.60%)  36 23/126 (18.25%)  28 10/126 (7.94%)  14
Gastrointestinal disorders       
Gastroenteritis  1  80/125 (64.00%)  160 85/126 (67.46%)  214 81/126 (64.29%)  178
Hepatobiliary disorders       
Hepatomegaly  1  53/125 (42.40%)  72 50/126 (39.68%)  72 52/126 (41.27%)  79
Infections and infestations       
AIDS encephalopathy  1  10/125 (8.00%)  10 15/126 (11.90%)  15 10/126 (7.94%)  10
Bronchiolitis  1  58/125 (46.40%)  83 66/126 (52.38%)  104 48/126 (38.10%)  76
Bronchopneumonia  1  9/125 (7.20%)  10 12/126 (9.52%)  13 12/126 (9.52%)  14
Candida nappy rash  1  17/125 (13.60%)  19 16/126 (12.70%)  19 14/126 (11.11%)  18
Candidiasis  1  29/125 (23.20%)  41 32/126 (25.40%)  38 17/126 (13.49%)  21
Gastroenteritis  1  52/125 (41.60%)  72 42/126 (33.33%)  61 47/126 (37.30%)  64
Impetigo  1  27/125 (21.60%)  37 26/126 (20.63%)  31 21/126 (16.67%)  24
Molluscum Contagiosum  1  9/125 (7.20%)  10 10/126 (7.94%)  11 10/126 (7.94%)  12
Mucocutaneous Herpes Simplex  1  8/125 (6.40%)  9 7/126 (5.56%)  8 9/126 (7.14%)  10
Oral Candidiasis  1  60/125 (48.00%)  101 46/126 (36.51%)  81 50/126 (39.68%)  58
Otitis Media  1  70/125 (56.00%)  140 81/126 (64.29%)  220 78/126 (61.90%)  154
Persistent Generalised Lymphadenopathy  1  13/125 (10.40%)  14 17/126 (13.49%)  19 21/126 (16.67%)  23
Pharyngitis  1  69/125 (55.20%)  112 65/126 (51.59%)  139 62/126 (49.21%)  118
Pneumonia  1  49/125 (39.20%)  81 44/126 (34.92%)  78 45/126 (35.71%)  78
Scabies  1  13/125 (10.40%)  15 28/126 (22.22%)  38 20/126 (15.87%)  25
TB  1  23/125 (18.40%)  24 28/126 (22.22%)  31 25/126 (19.84%)  25
Tinea  1  49/125 (39.20%)  63 50/126 (39.68%)  78 53/126 (42.06%)  81
Tonsilitis  1  41/125 (32.80%)  72 49/126 (38.89%)  89 39/126 (30.95%)  68
Urinary tract infection  1  10/125 (8.00%)  12 15/126 (11.90%)  21 6/126 (4.76%)  7
Varicella Zoster  1  7/125 (5.60%)  7 16/126 (12.70%)  16 5/126 (3.97%)  5
Investigations       
ALT Increased  1  11/125 (8.80%)  12 8/126 (6.35%)  10 4/126 (3.17%)  5
Gamma GT Increased  1  7/125 (5.60%)  7 4/126 (3.17%)  6 2/126 (1.59%)  3
Metabolism and nutrition disorders       
Failure to thrive  1  37/125 (29.60%)  41 31/126 (24.60%)  37 19/126 (15.08%)  23
Skin and subcutaneous tissue disorders       
Dermatitis  1  103/125 (82.40%)  320 96/126 (76.19%)  223 89/126 (70.63%)  206
Nappy rash  1  9/125 (7.20%)  10 19/126 (15.08%)  31 7/126 (5.56%)  10
1
Term from vocabulary, MedDRA 10.1
Indicates events were collected by systematic assessment
The CHER study did not include an early continuous therapy Arm, had not been powered to test for differences between early therapy 40 weeks vs. 96 weeks and never assessed in-utero vs. intrapartum infections.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr Avy Violari and Prof Mark Cotton
Organization: Perinatal HIV Research Unit, Johannesburg and Children’s Infectious Diseases Clinical Research Unit, Cape Town all in South Africa
Phone: 27 11 989 9702/27 21 938 4219 ext 9702/4219
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00102960     History of Changes
Other Study ID Numbers: CIPRA ZA 002
10404 ( Registry Identifier: DAIDS ES )
CHER ( Registry Identifier: DAIDS ES )
5R01AI062512-02 ( U.S. NIH Grant/Contract )
CIPRA-SA Project 2 ( Other Identifier: CIPRA )
First Submitted: February 4, 2005
First Posted: February 7, 2005
Results First Submitted: January 17, 2017
Results First Posted: November 30, 2018
Last Update Posted: November 30, 2018